Journal
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
Volume 24, Issue 2, Pages 177-190Publisher
SPRINGER
DOI: 10.1007/s11154-022-09777-y
Keywords
Pituitary adenoma; Pituitary tumor; Hallmarks of cancer; Invasion; Angiogenesis
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This review evaluates the biological processes underlying malignant transformation and their relevance to the development of pituitary adenomas. It addresses various processes such as genome instability, epigenetic reprogramming, angiogenesis, proliferative signals, immune evasion, and inflammation in relation to pituitary tumors. Additionally, it discusses the existence of oncogene-induced senescence in these tumors. Understanding these processes can provide insights into the resistance of pituitary tumors to malignant transformation and contribute to the development of novel anticancer treatments.
Over 20 years ago, Hanahan and Weinberg published a seminal review that addressed the biological processes that underly malignant transformation. This classical review, along with two revisions published in 2011 and 2022, has remain a classic of the oncology literature. Since many of the addressed biological processes may apply to non-malignant tumorigenesis, we evaluated to what extent these hallmarks pertain to the development of pituitary adenomas. Some of the biological processes analyzed in this review include genome instability generated by somatic USP8 and GNAS mutations in Cushing's diseases and acromegaly respectively; non-mutational epigenetic reprograming through changes in methylation; induction of angiogenesis through alterations of VEGF gene expression; promotion of proliferative signals mediated by EGFR; evasion of growth suppression by disrupting cyclin dependent kinase inhibitors; avoidance of immune destruction; and the promotion of inflammation mediated by alteration of gene expression of immune check points. We also elaborate further on the existence of oncogene induced senescence in pituitary tumors. We conclude that a better understanding of these processes can help us dilucidated why pituitary tumors are so resistant to malignant transformation and can potentially contribute to the development of novel anticancer treatments.
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